In 2015, revised diagnostic criteria were proposed by The International Panel for NMO Diagnosis (IPND). These guidelines are different depending on the AQP4 IgG antibody status of the person. The diagnostic requirements are more stringent in those without AQP4-IgG, and require 2 core clinical characteristics, one of which has to be optic neuritis, acute myelitis with longitudinally extensive transverse myelitis (LETM), or lesions in certain areas of the brain that cause typical NMOSD syndromes. Those who are AQP4-IgG positive require just one core clinical characteristic.
They also determined a set of “red flags” that do not exclude NMOSD if present, but may indicate another diagnosis. Some of these red flags include: a very short (less than 4 hours) or very long (more than 4 weeks) time to the worst part of an attack, and presence of oligoclonal bands in the cerebrospinal fluid.
They also give a list of neuroimaging characteristics of NMO, which include LETM, a lesion in the central part of the cord, and certain NMOSD-typical brain lesion patterns.
The IPND also stated that the characteristics of pediatric NMOSD are similar to adult NMOSD, and the proposed criteria can generally be used in this population, although they note that a LETM lesion is not as specific for NMOSD in children as it is in adults because LETM can occur in 15% of children with MS, and can occur in ADEM.
Furthermore, they note that 5-10% of NMOSD cases are monophasic, but note that it is unclear what criteria indicate that someone will maintain a monophasic disease course. They recommend that someone be considered to have monophasic NMOSD only after they have been relapse free for five or more years, but those who are AQP4-IgG positive should be considered to be at high risk for recurrence regardless of the length of time between attacks. A test for anti-MOG should be done as well.
Diagnostic criteria for NMOSD with AQP4-IgG
- At least 1 core clinical characteristic
- Positive test for AQP4-IgG using best available detection method (cell-based assay strongly recommended)
- Exclusion of alternative diagnoses
Diagnostic criteria for NMOSD without AQP4-IgG or unknown AQP4-IgG status
- At least 2 core clinical characteristic occurring as a result of one or more clinical attacks and meeting all of the following requirement:
- At least 1 core clinical characteristic must be optic neuritis, acute myelitis with LETM, or area postrema syndrome
- Dissemination in space (2 or more core clinical characteristic)
- Fulfillment of additional MRI requirements, as applicable
- Negative test for AQP4-IgG using best available detection method, or testing unavailable
- Exclusion of alternative diagnoses
Core clinical characteristics
- Optic neuritis
- Acute myelitis
- Area postrema syndrome: episode of otherwise unexplained hiccups or nausea and vomiting
- Acute brainstem syndrome
- Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions
- Symptomatic cerebral syndrome with NMOSD-typical brain lesions
Additional MRI requirements for NMOSD without AQP4-IgG or unknown AQP4-IgG status
- Acute optic neuritis: requires brain MRI showing
- normal findings or only nonspecific white matter lesions, OR
- optic nerve MRI with T2-hyperintense lesion or T1-weighted gadolinium-enhancing lesion extending over >1/2 optic nerve length or involving optic chiasm
- Acute myelitis: requires associated intramedullary MRI lesion extending over 3 or more contiguous segments (LETM) OR 3 or more contiguous segments of focal spinal cord atrophy in patients with history compatible with acute myelitis
- Area postrema syndrome: requires associated dorsal medulla/area postrema lesions
- Acute brainstem syndrome: requires associated periependymal brainstem lesions